There are various processings of powder or granular material, including granulating, drying, coating, and the like. Among them, as the granulating method of powder or granular material, can be listed the fluidized bed granulating method, agitation granulating method, centrifugal tumbling granulating method, and combinations thereof or combined-type granulating methods, and they are widely employed in various fields such as pharmaceutical preparations and food.
At first, among these granulating methods, the fluidized bed granulating method comprises sprinkling liquid material on powder or granular material, which has been in a fluidized state by dispersion and mixing within a processing vessel, increasing the grain sizes gradually. As a fluidized bed granulating apparatus for such processing, may be mentioned Flow Coater (trade name) by Freund Industrial Co., Ltd. which fundamentally comprises a processing vessel for containing and processing material to be processed, a fluidizing air supply device for supplying fluidizing air so as to fluidize the material, and a spray nozzle for spraying liquid on the material. By the fluidizing air, the material to be processed comes to be fluidized, and on this fluidized material, the liquid is sprayed by the spray nozzle, to carry out the granulation.
Next, the agitation granulating method comprises dispersing and mixing solid/liquid to produce particles, by agitation with an agitating blade (agitator). As an agitation granulating apparatus for such processing, be mentioned a high speed mixer FS-G model (trade name) of Fukae Kogyo Ltd., which is called, in another name, as a high speed mixing machine. As disclosed in Japanese Patent Publication No. 6-22667, Japanese Patent Publication No. 6-24619, Japanese Un-examined Patent Laid-Open No. 5-236, and Japanese Patent Publication No. 2-32932, this agitating granulating apparatus fundamentally comprises an agitating blade rotatably provided within a processing vessel, with a bottom portion of the processing vessel serving as a fixed wall. In addition to this construction, a disintegrating blade (chopper) may be provided if necessary, as shown in Japanese Un-examined Patent Laid-Open No. 5-115766, so that disintegration granulation may be performed by the chopper, in addition to tumbling granulation by the agitator. Further, if a drying process is needed, a vacuum drying system may be provided, or otherwise, a heater may be provided on the outer periphery of the processing vessel in a jacketing manner. Then, by suitably controlling rotational speed of the agitator and the chopper, quantity of the liquid, quantity of charging, granulation time, temperature, and the like, mixing granulation of the powder or granular material is carried out.
On the other hand, the centrifugal tumbling method comprises tumbling mixing of powder material on a rotating disk, while spraying liquid on the material to make powder particles adhere to and agglomerate with one another. As a centrifugal tumbling granulating apparatus for such processing, be mentioned CF Granulator (trade name) made by Freund Industrial Co., Ltd., an automatic coating apparatus described in Japanese Patent Publication No. 54-992, and a granulating apparatus of Japanese Un-examined Patent Laid-Open No. 6-262054 (corresponding to U.S. Pat. No. 5,507, 871), and each of these apparatus fundamentally comprises a rotating disk, which rotates generally horizontally, provided at a bottom portion of a processing vessel. If necessary, slit air is supplied into the inside of the processing vessel through a ring-shaped gap formed between circumference of the rotating disk and a inside wall portion of the processing vessel, while dispersing powder and spraying liquid on the material to be processed within the processing vessel, so as to perform granulation of the powder or granular material.
Further, there has been used the combined-type granulating method which combines the above-described techniques. For example, there has been appeared an apparatus, such as Spir-A-Flow (trade name) made by Freund Industrial Co., Ltd., which fundamentally performs the fluidized bed granulation, and suitably combines it with the agitation granulation and the centrifugal tumbling granulation, using combination of a rotor disk and an agitator.
In such process of granulating powder or granular material, from the viewpoint of the object of producing particles and from the viewpoint of process validation for a product, measurement and control of particle diameter are so important as to be incomparable with the other factors. By this reason, various granulating apparatuses use a moisture meter, a pressure gauge, an electric power meter, and the like as sensors for process validation. Using these sensors, an end of granulation, granulating conditions, and the like are controlled. Here, "process validation" is defined as "a documented program giving a high-level assurance that a certain process constantly produces products compliant with preset standard and quality characteristics", and is important from the viewpoint of GMP (Good Manufacturing Practice).
However, measurement using these sensors gives only indirect "estimation" of particle diameters, and has disadvantage that error becomes large. Further, according to a granulation method, the above-described sensors may not be used. For example, in non-water type granulation using ethanol, the moisture meter can not be used. Further, each granulating method has following specific difficulty.
First, in the fluidized bed granulating method, process control generally uses an infrared absorption moisture meter such as Moiswatch (trade name) made by Okawaraseisakusho. Such a moisture meter, however, has disadvantages in that data is blurred in high moisture content area, and that variation of moisture content is smaller in comparison with variation of particle diameter. Further, in the case of granulation with constant moisture content, the end point of granulation can not be decided by such a moisture meter.
Next, in the case of the agitation granulating method, although there exist examples of validation using a pressure gauge or a resistance meter or based on power consumption, granulation is generally controlled by charge amount of raw material, added amount of binder, rotation speed of the agitating blade, and agitating time. For example, in the case of the control by power consumption, power consumption rapidly increases at the start of the granulation, repeats fluctuations as the granulation proceeds, decreases gradually as resistance to agitation decreases, and becomes steady state as the regulation of particles proceeds, and, following these stages, the end point of the granulation is decided. However, synthetic process or storage conditions of the raw material etc. may affect them so that the raw material etc. are varied in their hygroscopic property (wettability), fluidity, and powder property (characteristics of bulk) such as agglomeration or adhesion property etc. Accordingly, for validation, it is desirable to control by feedback. Further, as in the case of the control by power consumption, when granulation is made to proceed until change of load on a granulating apparatus becomes obvious, detection by a sensor is easy, but granulation tends to proceed excessively. In particular, in the case of granulation for tabletting, the excessive granulation makes the particles too hard, or produces too small amount of fine powder.
Further, in the centrifugal tumbling granulating method, an operator decides the end point of the granulation by directly feeling water content in the powder material with his hand, or by observing sampled products with a magnifying lens, for example. Judgment, however, by the operator's feeling or eye observation can not be said as objective judgment at all, and validation is impossible. On the other hand, although introduction of a moisture meter or a lever resistance type pressure gauge has been studied, a satisfactory result has not been obtained since, for example, measurement error becomes large due to adherence of the powder material to an employed sensor such as a moisture meter. In particular, in the case of an electrode-type moisture meter, powder adheres to surface of an electrode of the moisture meter, and the measurement becomes impossible in short time. In addition, a moisture meter or the like has been used mainly for maintaining of an equilibrium state of granulation process, and can not be used for deciding an end point of granulation.
Thus, there are various disadvantages for control of granulation process in respective granulating methods. In particular, the fluidized bed granulating method has a disadvantage in that variation in grain size and particle shape (referred to as "grain size etc." in abbreviation) of products is large, and various grain size control methods have been tried for this granulating method.
In that case, to make the grain size etc. of powder or granular material uniform, it is necessary to monitor the grain size etc. always in real time for change of processing conditions at any time, and to suitably decide an end point of processing for obtaining products with desired properties. For that purpose, as described above, such techniques as time management by timer control, observation by a skilled worker, control by water content value, and the like have been employed. However, the timer control or the observation by a skilled worker has a problem in accuracy. Namely, the timer control can not cope with change in bulk characteristics, and variation in product grain size can not be avoided. Further, accuracy is lacked in workings depending on skilled worker's experience or perception such as judgment of the processing state by observing the inside of a processing apparatus through its inspection hole. Further, it is difficult to give exact judgment by the control based on water content value, since change of water content does not quickly respond to rapid advance of granulation in the stage approaching the end point of the granulation. Accordingly, in many conventional cases, end of granulation is decided by judgment of grain size etc. by eye observation or measurement of granulated objects sampled in the course of the granulation process. For example, the end point is predicted by sieving the sampled products with 16 mesh sieve for 10 seconds, and by calculating based on the ratio of the particles remaining on the sieve.
Such a method, however, can not obtain data in real time, is inferior in accuracy and rapidity, and, thus, is unfavorable from the viewpoint of validity. Accordingly, to grasp, in real time, grain size etc. simply and accurately, such grain size measurement devices have been proposed as described in Japanese Un-examined Patent Laid-Open No. 4-265142, Japanese Un-examined Patent No. 7-794, Japanese Un-examined Patent Laid-Open No. 7-120374, and Japanese Un-examined Patent Laid-Open No. 8-131810.
Here, in the grain size measurement device of 4-265142, a processing vessel (granulating vessel) is provided with a drawing tube for powder or granular material, and high pressure gas is blown from the inside of the processing vessel to introduce the powder or granular material within the processing vessel into the drawing tube. Thus-introduced powder or granular material is captured by adhesive film provided in an inner part of the drawing tube, and an image of the captured powder or granular material is picked up to measure its grain size etc. After the measurement of the grain size, the inside of the drawing tube for powder or granular material is cleaned by negative pressure in the processing vessel. On the other hand, in the device of 7-794, a camera device and a high speed stroboscopic device are provided being directed toward the inside of the processing vessel, and, using these devices, a static image is obtained to measure grain size etc.
Further, as for the camera devices for granulation, coating, or the like in 7-120374 and 8-131810, camera system devices and lighting system devices are arranged within the processing vessel, and powder or granular material is made to be in a separated state by air and, then, is photographed. In that case, in the camera device of 7-120374, front end portions of the camera system and the lighting system are provided adjacently within the processing vessel, and air is supplied in the direction of photographing and in the direction at right angles with the former to put the powder or granular material in the separated state. On the other hand, in 8-131810, lighting and air injection are given obliquely in front of a lens tube containing the camera system, thus putting the powder or granular material in dispersed condition to take a picture.
Although these devices, in particular the grain size measurement device of 4-265142, are superior ones which can measure grain size etc. in real time simply and accurately, when the inside of the processing vessel is not at negative pressure, sometimes a great amount of powder or granular material adheres to the adhesive film so that it becomes impossible to measure. Further, the powder or granular material introduced in the last time remains within the drawing tube, and adheres to the adhesive film together with the powder or granular material introduced in the next time so that accurate sample can not be obtained.
Further, at the time of measurement, the adhesive film for capturing the powder or granular material is tightly fixed to the drawing tube. For next measurement, however, it should be once separated from the drawing tube and wound, so that unused portion of the film is moved to the suitable position. Thus, at the time of the movement of the film, there exist gaps between the adhesive film and the drawing tube for powder or granular material, and the powder or granular material flows out through these gaps, contaminating adjacent portions of the device and an unused portion of the adhesive film. In that case, the flowed-out powder or granular material is scattered onto the image pick-up means for obtaining sampling images, having an adverse effect on subsequent pick-ups and measurements, or making measurement itself impossible, and settlement of these problems has been desired.
On the other hand, the devices of 7-120374 and 8-131810 photograph particles by dispersing them with purging air. Thus, in an apparatus where particles are floated such as the fluidized bed apparatus, it is possible to disperse the particle, and the device of 7-120374 or 8-131810 can be used without problem for photographing particles. However, in the agitation granulating apparatus and the centrifugal tumbling granulating apparatus, a great amount of particles are in a concentrated state, and it is difficult to disperse the particles to identify an individual, and the device of 7-120374 or 8-131810 can not be applied to such a kind of granulating apparatus.
An object of the present invention is to provide a particle measurement device which can perform real-time and highly-reliable measurement of grain size etc. in various granulating apparatuses.
The above-described and other objects and new features of the present invention will be obvious from the following description and the attached drawings.